Journal article
Known allosteric proteins have central roles in genetic disease
G Abrusán, DB Ascher, M Inouye
Plos Computational Biology | Published : 2022
Abstract
Allostery is a form of protein regulation, where ligands that bind sites located apart from the active site can modify the activity of the protein. The molecular mechanisms of allostery have been extensively studied, because allosteric sites are less conserved than active sites, and drugs targeting them are more specific than drugs binding the active sites. Here we quantify the importance of allostery in genetic disease. We show that 1) known allosteric proteins are central in disease networks, contribute to genetic disease and comorbidities much more than non-allosteric proteins, and there is an association between being allosteric and involvement in disease; 2) they are enriched in many ma..
View full abstractGrants
Awarded by British Heart Foundation
Awarded by BHF Cambridge Centre of Research Excellence
Awarded by NIHR Cambridge Biomedical Research Centre
Awarded by NHMRC
Funding Acknowledgements
G.A. and M.I were supported by the Cambridge-Baker Systems Genomics Initiative. M. I. was supported by the Munz Chair of Cardiovascular Prediction and Prevention. This work was supported by core funding from the: British Heart Foundation (RG/13/13/30194; RG/18/13/33946), BHF Cambridge Centre of Research Excellence (RE/13/6/30180), and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).. It was also supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. Additionally, this work was supported by the NHMRC GNT1174405 grant for D.A. and in part by the Victorian Government's Operational Infrastructure Support Program. The authors declare no competing interests.. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.